Hi Dr. Sherer:

Does HIV still replicate or mutates even though a person is undetectable?

Thank you.

Yes. Even in the presence of a viral load below 50 copies/ml, there is evidence of ongoing replication in sequestered sites of HIV infection such as the central nervous system and the gonads. Different viral evolution patterns have been observed in different sites in the same person over time.

A study presented at the recent resistance meeting used an ultra-sensitive VL test to look at low-level viremia (149 c/mL). It is unknown whether this level of viremia reflects ongoing virus replication or release of virus from long-lived, chronically infected cells. When the ART regimens were intensified, no change was observed in the level of low-level viremia. The authors concluded that low-level viremia does not reflect ongoing rounds of viral replication, and rather probably represents continued production of virus by long-lived chronically infected calls. An alternative is that virus production in sanctuary sites not penetrated by drug was responsible for the low level viremia.

The useful information in the study appeared to be that more intensive ART would not be helpful to reduce or eliminate low level viremia at levels of 1-49 copies/ml. Whether this means that ongoing replication and mutations are less likely remains to be seen. Unfortunately for clinicians and patients, we still have to assume that some ongoing replication and mutations ARE taking place in sequestered sites, and thus ongoing resistance may be 'inevitable', at least in some patients.

The most reassuring data to contradict, or at least limit the impact of, that possibility is the existence of patients in long term cohorts on stable ART with excellent control, full virologic suppression, and good health for 7 years or more.

Patients and clinicians can be reassured that if they do their jobs well, choose the proper initial regimen and take the medications as prescribed with excellent adherence, the chances of a positive response with complete virologic control and no drug resistance is high, involving a majority of patients treated after 3-7 years.